Synthesis of [¹⁸F]Fluoroarenes by Nucleophilic Radiofluorination of N‐Arylsydnones

Abstract

A practical method for radiofluorination of anilines with [18F]fluoride via N-arylsydnone intermediates is described. These precursors are stable, easy to handle and facilitate direct and regioselective 18F-labeling to prepare [18F]fluoroarenes. The value of this methodology is further highlighted by successful application to prepare an 18F-labeled neuropeptide.

Direct arene C–H fluorination with 18 F − via organic photoredox catalysis

“…Thus, modern radiofluorination methods have sought to generalize the arene scope for this transformation. Current strategies include 18 F-deoxyfluorination of phenols via uronium (11) and N-arylsydnone (12) intermediates; displacement of sulfonium salts (13); fluorodemetalation of preformed palladium or nickel arene complexes from the requisite aryl halides or boronic acids (14,15); and copper-mediated cross-coupling of preformed or in situ-generated aryliodoniums (16,17), aryl boronic acids (18), esters (19), and arylstannanes (20) (Fig. 1A).…”

Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions

“…Murphy and co‐workers developed N ‐arylsydnones as novel precursors for the 18 F‐labeling of arenes bearing electron‐deficient substituents (Scheme B) . It was found that the sydnone was not only inductively more electron withdrawing than the nitro group, but was also positioned away from the aryl plane and limited full resonance with the arene.…”

Chemie der Positronenemissionstomographie: Aktuelle Fortschritte bei 11C‐, 18F‐, 13N‐ und 15O‐Markierungsreaktionen

“…Murphy et al. entwickelten N ‐Arylsydnone als neue Vorstufen für die 18 F‐Markierung von Arenen mit elektronenarmen Substituenten (Schema B) . Es wurde festgestellt, dass das Sydnon nicht nur induktiv stärker elektronenziehend ist als die Nitrogruppe, sondern sich auch abseits der Aryl‐Ebene befindet und keine vollständige Resonanz mit dem Aren eingeht.…”